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2016 Grants - Teich

A Cross-Species Study of DNA Methylation in Alzheimer’s Disease Dementia

Andrew Teich, M.D., Ph.D.
Columbia University Medical Center
New York, New York

2016 New Investigator Research Grant

How are gene patterns changed during the development of Alzheimer’s disease?

Background
A major focus of Alzheimer’s disease research is to identify genetic factors that may increase the risk of developing the disease. In addition to examining specific genes that increase risk, researchers are also studying other types of unique genetic information. The epigenome, for example, is a record of chemical modifications that can turn genes “on” or “off” in response to their environment or disease state. Scientists now suspect that in people with Alzheimer’s disease, these modifications may become altered in ways that contribute to disease progression. This chemical modification of genetic material (DNA) is known as epigenetics.

One way in which DNA is modified is by the addition of a chemical methyl group – a process called methylation. DNA methylation may be involved in many normal brain processes, including learning and memory. More research is needed to determine if alterations in the methylation of genes that are important for memory may contribute to Alzheimer’s disease.

Research Plan
For their current research project, Dr. Teich and colleagues will study patterns of DNA methylation in the brains of mice genetically engineered to have an Alzheimer’s-like condition. They will determine if certain genes important for learning and memory show abnormal patterns of methylation in Alzheimer’s-like mice when compared to mice with normal cognition. The researchers will then compare the patterns of DNA methylation in the Alzheimer’s-like mice with patterns in human brain samples from people who had Alzheimer’s disease. This comparison will allow the researchers to specifically determine which genes are abnormally methylated in Alzheimer’s disease and then study their function in detail.

Impact
The research proposed by Dr. Teich may lead to the identification of specific changes in DNA that are linked to the development of Alzheimer’s disease. The results of this work could shed new light on epigenetic factors that could be targeted for the development of novel Alzheimer’s treatments.